title: Characterization of different osteosarcoma phenotypes by PET imaging in preclinical animal models.
abstract: The aim of this study was to characterize the different phenotypes of osteosarcoma by PET, comparing the uptake of 3 tracers ((18)F-FDG, (18)F-fluoromisonidazole [(18)F-FMISO], and (18)F-fluoride) in preclinical mouse models that reflect the heterogeneity of the human disease.
  
  
  METHODS
  Mouse LM8 osteosarcoma, human 143B, and Caprin-1 stably overexpressing SaOS-2 cells were injected intratibially in C3H and severe-combined immunodeficient mice. PET imaging with (18)F-FDG, (18)F-FMISO, and (18)F-fluoride was performed in these mouse models, and a ratio between the standardized uptake value of the primary tumor and a control area of bone was calculated and compared among the models. Histology and immunohistochemistry were performed to confirm the PET findings.
  
  
  RESULTS
  The pattern of tracer uptake differed among the primary tumors of the 3 models in accordance with the histology and immunohistochemistry on primary tumor sections. The osteolytic tumors in the 143B model showed the highest uptake of (18)F-FDG, an indicator of glucose metabolism, which was significantly higher (P < 0.05) than in the SaOS-2/Caprin-1 model and correlated with the percentage of Ki67-positive cells in the primary tumors. Hypoxia, indicated by (18)F-FMISO accumulation, was higher in the SaOS-2/Caprin-1 and 143B cell line-derived tumors (P < 0.01). Finally (18)F-fluoride, a marker of bone remodeling, correlated with the osteoblastic phenotype. The SaOS-2/Caprin-1 cell-derived tumors showed a significantly higher uptake than the moderately osteoblastic LM8 (P < 0.05) and the osteolytic 143B (P < 0.01) cell line-derived tumors.
  
  
  CONCLUSIONS
  Differential PET imaging with tracers indicating metabolic activity, hypoxia, or bone remodeling will be helpful for the characterization of different osteosarcoma phenotypes and subsequent evaluation of more specific treatment modalities targeting the processes that are predominant in each specific tumor type or subtype.
authors.affiliation: Laboratory for Orthopaedic Research, Department of Orthopaedics, Balgrist University Hospital, Zurich, Switzerland.
authors.forename: Carmen
authors.initials: C
authors.lastname: Campanile
authors.forename: Matthias J E
authors.initials: MJ
authors.lastname: Arlt
authors.forename: Stefanie D
authors.initials: SD
authors.lastname: Krämer
authors.forename: Michael
authors.initials: M
authors.lastname: Honer
authors.forename: Ana
authors.initials: A
authors.lastname: Gvozdenovic
authors.forename: Patrick
authors.initials: P
authors.lastname: Brennecke
authors.forename: Cindy R
authors.initials: CR
authors.lastname: Fischer
authors.forename: Adam A
authors.initials: AA
authors.lastname: Sabile
authors.forename: Adrienne
authors.initials: A
authors.lastname: Müller
authors.forename: Simon M
authors.initials: SM
authors.lastname: Ametamey
authors.forename: Walter
authors.initials: W
authors.lastname: Born
authors.forename: Roger
authors.initials: R
authors.lastname: Schibli
authors.forename: Bruno
authors.initials: B
authors.lastname: Fuchs
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D019008:Drug Resistance, Neoplasm; D005260:Female; D005459:Fluorides; D019788:Fluorodeoxyglucose F18; D006801:Humans; D051379:Mice; D008920:Misonidazole / Q000031:analogs & derivatives; D010006:Osteoblasts / Q000473:pathology; D010010:Osteoclasts / Q000473:pathology; D012516:Osteosarcoma / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D049268:Positron-Emission Tomography; D013977:Tibia / Q000473:pathology
chemical_list: C031843:fluoromisonidazole; D019788:Fluorodeoxyglucose F18; D008920:Misonidazole; D005459:Fluorides
keywords: osteoblastic; osteolytic; osteosarcoma; positron emission tomography